| Abstract: | Correlation studies on patients with myasthenia gravis are reported in which clinical assessment of fatigue and neurophysiological findings are compared to blood levels of pyridostigmine. Measurements using a high-pressure liquid chromatography method (HPLC), give reproducible results. The levels of pyridostigmine in the serum or plasma of healthy controls and of patients show no essential differences. Components of coffee, tea, chocolate and cigarettes can markedly disturb the chromatography by adding additional peaks, so that interpretation becomes difficult or impossible. Blood levels can be measured approximately one hour after oral intake of 60 mg pyridostigmine. Concentrations rise for two to four hours and then decline exponentially. The half-life of pyridostigmine was between 156 and 210 minutes. Despite identical oral dosages, the concentration differed intraindividually and interindividually among patients. While the blood level does not reach its maximum value for 1-1 1/2 to 3 hours, the maximum clinical and neurophysiological effect of pyridostigmine appears 30-60 minutes after ingestion. Variable distribution of cholinesterase inhibitors over the different compartments (blood, synaptic region) is assumed to cause this temporal lag. If the total amount of pyridostigmine is divided into 4-5 doses, the concentration profiles over the course of a day are relatively stable. There is no significant correlation between the variations in blood level throughout one day, and changes in myasthenic symptomatology. Effects of pyridostigmine can be measured at levels as low as 5 ng/ml; at levels above 40 ng/ml further improvement can be detected only rarely. Blood levels were lower if corticosteroids were administered simultaneously; azathioprine had no influence on blood levels. Blood levels assays allow better differentiation of cholinergic and myasthenic crises and the identification of disturbed absorption and interactions with other medications. |
